(6-Methylpyridin-3-yl)methanol

Chemical Properties

White Solid

Uses

(6-Methylpyridin-3-yl)methanol is a reactant used in the preparation of pioglitazone (P471000) metabolites.

Uses

5-Hydroxymethyl-2-methylpyridine is a reactant used in the preparation of pioglitazone (P471000) metabolites.

Synthesis

General procedure for the synthesis of 6-methyl-3-methanolpyridine from 6-methylnicotinic acid methyl ester: To a stirred solution of 6-methylnicotinic acid methyl ester (21 g; 140 mmol; 1 eq.) in anhydrous THF (150 mL) was added slowly and dropwise to a THF solution (210 mL; 210 mmol; 1.5 eq.) of 1 M LiAlH4 at -5 °C. After the dropwise addition, the reaction mixture was continued to be stirred at 23 °C for 2 hours. Subsequently, the mixture was cooled to -10 °C and the reaction was carefully quenched with sodium sulfate decahydrate and ethyl acetate until bubbling ceased. The mixture was filtered through a pad of diatomaceous earth and the filtrate was concentrated to dryness under reduced pressure to afford 6-methyl-3-methanolpyridine (17 g, 100% yield). The product was characterized by 1H NMR (DMSO-d6): δ 8.37 (s, 1H), 7.59 (dd, 1H, J = 2,8Hz), 7.19 (d, 1H, J = 8Hz), 5.22 (t, 1H, J = 6Hz), 4.47 (d, 2H, J = 6Hz), 2.45 (s, 3H).

References

[1] Patent: WO2015/95128, 2015, A1. Location in patent: Paragraph 0152; 0155; 0156
[2] Organic Preparations and Procedures International, 2015, vol. 47, # 3, p. 220 - 226
[3] Patent: US2005/124586, 2005, A1. Location in patent: Page/Page column 7
[4] Journal of the Chemical Society. Perkin Transactions 2, 2002, # 5, p. 928 - 937
[5] Patent: WO2018/165718, 2018, A1. Location in patent: Page/Page column 100; 101; 102